title: Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors.
abstract: MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role in the regulation of gene expression during carcinogenesis. The role of miRNAs in breast cancer has been thoroughly investigated, and although many miRNAs are identified as cancer related, little is known about their involvement in benign tumors. In this study, we investigated miRNA expression profiles in the two most common types of human benign tumors (fibroadenoma/fibroadenomatosis) and in malignant breast tumors and explored their role as oncomirs and tumor suppressor miRNAs. Here, we identified 33 miRNAs with similar deregulated expression in both benign and malignant tumors compared with the expression levels of those in normal tissue, including breast cancer-related miRNAs such as let-7, miR-21 and miR-155. Additionally, messenger RNA (mRNA) expression profiles were obtained for some of the same samples. Using integrated mRNA/miRNA expression analysis, we observed that overexpression of certain miRNAs co-occurred with a significant downregulation of their candidate target mRNAs in both benign and malignant tumors. In support of these findings, in vitro functional screening of the downregulated miRNAs in non-malignant and breast cancer cell lines identified several possible tumor suppressor miRNAs, including miR-193b, miR-193a-3p, miR-126, miR-134, miR-132, miR-486-5p, miR-886-3p, miR-195 and miR-497, showing reduced growth when re-expressed in cancer cells. The finding of deregulated expression of oncomirs and tumor suppressor miRNAs in benign breast tumors is intriguing, indicating that they may play a role in proliferation. A role of cancer-related miRNAs in the early phases of carcinogenesis and malignant transformation can, therefore, not be ruled out.
authors.affiliation: Department of Clinical Molecular Biology (EpiGen), Division of Medicine and Laboratory Sciences, Akershus University Hospital and.
authors.forename: Andliena
authors.initials: A
authors.lastname: Tahiri
authors.forename: Suvi-Katri
authors.initials: SK
authors.lastname: Leivonen
authors.forename: Torben
authors.initials: T
authors.lastname: Lüders
authors.forename: Israel
authors.initials: I
authors.lastname: Steinfeld
authors.forename: Miriam
authors.initials: M
authors.lastname: Ragle Aure
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisler
authors.forename: Rami
authors.initials: R
authors.lastname: Mäkelä
authors.forename: Silje
authors.initials: S
authors.lastname: Nord
authors.forename: Margit L H
authors.initials: ML
authors.lastname: Riis
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.forename: Kristine
authors.initials: K
authors.lastname: Kleivi Sahlberg
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Merja
authors.initials: M
authors.lastname: Perälä
authors.forename: Ida R K
authors.initials: IR
authors.lastname: Bukholm
authors.forename: Vessela N
authors.initials: VN
authors.lastname: Kristensen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger; D012016:Reference Values
chemical_list: C552722:MIRN195 microRNA, human; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger